Keloids are dermal tumors which occur in response to trauma. A hereditary predisposition to Keloid formation occurs with high frequency in Black populations. In addition to over-proliferation of fibroblasts this tumor growth involves abnormal collagen metabolism. The goals of these studies are to identify the primary gene defect causing this condition, its mode of action, and those environmental factors which alter its expression. The strategy used in this investigation is to search for patterns of differences in cell culture between fibroblasts derived from keloids and from normal scars and skin. We have found that cultured fibroblasts isolated from normal and keloid tissue are similar in regard to both growth characteristics and rate of collagen synthesis; however, the addition of physiological levels of hydrocortisone to the culture media results in significant differences between these cell types in both their growth characteristics and rate of collagen synthesis and growth in keloid cells. The studies described here are aimed at elucidating the regulatory mechanism functioning abnormally in keloids and the relationship between the abnormal phenotypes observed, namely collagen metabolism and cell growth by determining (1) the genetic and epigenetic contributions to these phenotypes; (2) whether the phenotypes are cell limited and the dominance relationships between them; (3) the mechanisms of the response to hydrocortisone by studying collagen types involved, aspects of collagen synthesis and degradation, changes in other matrix components, and the roles of prostaglandin and cyclic nucleotides; (4) the ability of other environmental variables to elicit or prevent differences between normal and keloid fibroblasts. The feasibility of using human skin grafts on nude mice as an animal model of keloid formation will be investigated to permit in vivo analysis of the phenotypic abnormalities detected in vitro and the testing of possible treatments.